Biology:Gelatinase B
| Gelatinase B | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC number | 3.4.24.35 | ||||||||
| CAS number | 146480-36-6 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||||
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Gelatinase B (EC 3.4.24.35, 92-kDa gelatinase, matrix metalloproteinase 9, type V collagenase, 92-kDa type IV collagenase, macrophage gelatinase, 95 kDa type IV collagenase/gelatinase, collagenase IV, collagenase type IV, gelatinase MMP 9, MMP 9, type IV collagen metalloproteinase) is an enzyme.[1][2][3] This enzyme catalyses the following chemical reaction
- Cleavage of gelatin types I and V and collagen types IV and V
This enzyme is similar to gelatinase A, but possesses a further domain. Regarding its structure, Gelatinase B has domains which can bind with gelatin, laminin, and collagens type I and IV- collagenases do not possess these binding domains.[4]
Function
Due to its role in cleaving collagen in the extracellular matrix, gelatinase B has multiple functional roles in normal physiology.
Neutrophil action
Gelatinase B, along with elastase, appears to be a regulatory factor in neutrophil migration across the basement membrane.[5] Gelatinase B plays several important functions within neutrophil action, such as degrading extracellular matrix, activation of IL-1β, and cleavage of several chemokines.[6] In a mouse model, Gelatinase B deficiency resulted in resistance to endotoxin shock, suggesting that Gelatinase B is important in sepsis.[7]
Angiogenesis
Gelatinase B may play an important role in angiogenesis and neovascularization. For example, gelatinase B appears to be involved in the remodeling associated with malignant glioma neovascularization.[8] It is also a key regulator of growth plate formation—both growth plate angiogenesis and the generation of hypertrophic chondrocytes. Knock-out models of Gelatinase B result in delayed apoptosis, vascularization, and ossification of hypertrophic chondrocytes.[9] Lastly, there is significant evidence that Gelatinase B is required for the recruitment of endothelial stem cells, a critical component of angiogenesis [10]
Wound repair
In in vitro experiments, it has been demonstrated that gelatinase B is greatly upregulated during human respiratory epithelial healing.[11] Using a gelatinase B deficient mouse model, it was seen that gelatinase B coordinated epithelial wound repair and deficient mice were unable to remove the fibrinogen matrix during wound healing.[12] When interacting with TGF-ß1, Gelatinase B also stimulates collagen contraction, aiding in wound closure.[13]
Pathology
Gelatinase B has been found to be associated with numerous pathological processes, including immunologic and vascular diseases. For example, it has been implicated in the development of aortic aneurysms,[14] and its disruption prevents the development of aortic aneurysms.[15] Elevated gelatinase B levels can also be found in the cases of rheumatoid arthritis[16] and focal brain ischemia.[17]
However, one of its most widely studied associated pathology is the relationship between Gelatinase B and cancer, due to its role in extracellular matrix remodeling and angiogenesis. For example, its increased expression was seen in a metastatic mammary cancer cell line.[18] A.R. Farina and others have argued that Gelatinase B plays a central role in tumor progression, from angiogenesis, to stromal remodeling, and ultimately metastasis.[19] However, because of its physiologic function, it may be difficult to leverage Gelatinase B inhibition into cancer therapy modalities. However, Gelatinase B has been investigated in tumor metastasis diagnosis—complexes of Gelatinase B/Tissue Inhibitors of Metalloproteinases are seen to be increased in gastrointestinal cancer and gynecologic malignancies [20]
See also
References
- ↑ "Expression of a metalloproteinase that degrades native type V collagen and denatured collagens by cultured human alveolar macrophages". The Journal of Clinical Investigation 80 (6): 1644–50. Dec 1987. doi:10.1172/jci113253. PMID 3680518.
- ↑ "SV40-transformed human lung fibroblasts secrete a 92-kDa type IV collagenase which is identical to that secreted by normal human macrophages". The Journal of Biological Chemistry 264 (29): 17213–21. Oct 1989. PMID 2551898.
- ↑ "Secretion and glycosylation of rabbit macrophage type V collagenase". Matrix 10 (2): 84–90. May 1990. doi:10.1016/s0934-8832(11)80174-5. PMID 2165210.
- ↑ "Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9)". Critical Reviews in Biochemistry and Molecular Biology 37 (6): 375–536. Dec 2002. doi:10.1080/10409230290771546. PMID 12540195.
- ↑ "Role of gelatinase B and elastase in human polymorphonuclear neutrophil migration across basement membrane". American Journal of Respiratory Cell and Molecular Biology 14 (3): 288–95. Mar 1996. doi:10.1165/ajrcmb.14.3.8845180. PMID 8845180.
- ↑ "Gelatinase B functions as regulator and effector in leukocyte biology". Journal of Leukocyte Biology 69 (6): 851–9. Jun 2001. PMID 11404367.
- ↑ "Gelatinase B deficiency protects against endotoxin shock". European Journal of Immunology 32 (8): 2163–71. Aug 2002. doi:10.1002/1521-4141(200208)32:8<2163::aid-immu2163>3.0.co;2-q. PMID 12209628.
- ↑ "Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas". British Journal of Cancer 79 (11–12): 1828–35. Apr 1999. doi:10.1038/sj.bjc.6690291. PMID 10206300.
- ↑ "MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes". Cell 93 (3): 411–22. May 1998. doi:10.1016/s0092-8674(00)81169-1. PMID 9590175.
- ↑ "Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand". Cell 109 (5): 625–37. May 2002. doi:10.1016/s0092-8674(02)00754-7. PMID 12062105.
- ↑ "Gelatinase B is involved in the in vitro wound repair of human respiratory epithelium". Journal of Cellular Physiology 166 (2): 413–26. Feb 1996. doi:10.1002/(sici)1097-4652(199602)166:2<413::aid-jcp20>3.0.co;2-a. PMID 8592002.
- ↑ "Matrix metalloproteinase gelatinase B (MMP-9) coordinates and effects epithelial regeneration". The Journal of Biological Chemistry 277 (3): 2065–72. Jan 2002. doi:10.1074/jbc.m107611200. PMID 11689563.
- ↑ "Matrix metalloproteinase-9 activates TGF-β and stimulates fibroblast contraction of collagen gels". American Journal of Physiology. Lung Cellular and Molecular Physiology 306 (11): L1006–15. Jun 2014. doi:10.1152/ajplung.00015.2014. PMID 24705725.
- ↑ "Identification of matrix metalloproteinases 3 (stromelysin-1) and 9 (gelatinase B) in abdominal aortic aneurysm". Arteriosclerosis and Thrombosis 14 (8): 1315–20. Aug 1994. doi:10.1161/01.atv.14.8.1315. PMID 8049193.
- ↑ "Targeted gene disruption of matrix metalloproteinase-9 (gelatinase B) suppresses development of experimental abdominal aortic aneurysms". The Journal of Clinical Investigation 105 (11): 1641–9. Jun 2000. doi:10.1172/jci8931. PMID 10841523.
- ↑ "Markedly elevated serum MMP-9 (gelatinase B) levels in rheumatoid arthritis: a potentially useful laboratory marker". Clinical Immunology and Immunopathology 78 (2): 161–71. Feb 1996. doi:10.1006/clin.1996.0025. PMID 8625558.
- ↑ "Increased gelatinase A (MMP-2) and gelatinase B (MMP-9) activities in human brain after focal ischemia". Neuroscience Letters 238 (1–2): 53–6. Nov 1997. doi:10.1016/s0304-3940(97)00859-8. PMID 9464653.
- ↑ "The alpha 3 beta 1 integrin is associated with mammary carcinoma cell metastasis, invasion, and gelatinase B (MMP-9) activity". International Journal of Cancer 87 (3): 336–42. Aug 2000. doi:10.1002/1097-0215(20000801)87:3<336::aid-ijc5>3.3.co;2-v. PMID 10897037.
- ↑ "Gelatinase B/MMP-9 in Tumour Pathogenesis and Progression". Cancers 6 (1): 240–96. 2014. doi:10.3390/cancers6010240. PMID 24473089.
- ↑ "Plasma assay of gelatinase B: tissue inhibitor of metalloproteinase complexes in cancer". Cancer 76 (4): 700–8. Aug 1995. doi:10.1002/1097-0142(19950815)76:4<700::aid-cncr2820760426>3.0.co;2-5. PMID 8625169.
External links
- Gelatinase+B at the US National Library of Medicine Medical Subject Headings (MeSH)
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